The transformation of roxarsone (ROX) during UV disinfection with Fe(III) has been investigated. Fe(OH)2+, as the main Fe(III) species at pH = 3, produces HO[rad] under UV irradiation leading to the oxidation of ROX. Dissolved oxygen plays a very important role in the continuous conversion of generated Fe2+ to Fe3+, which ensures a Fe(III)-Fe(II) cycle in the system. The presence of Cl−/HCO3 −/NO3 − has little influence on the ROX transformation, whereas PO4 3− achieves an obvious inhibitory effect. The transformation of ROX leads to the formation of inorganic arsenic consisting of a much higher amount of As(V) than As(III). LC-MS analysis shows that phenol, o-nitrophenol and arsenic acid were the main transformation products. Both the radical scavenger experiment and electron spin resonance data confirm that the HO[rad] is responsible for ROX transformation. The toxic transformation products are found to have potential environmental risks for the natural environment, organisms and human beings.